The fibroblast growth factors (FGFs) are a group of structurally related peptides with at least 23 family members identified to date. FGFs specify the differentiation, patterning, and proliferation of a variety of tissues. FGF-8 is thought to play a role in limb bud patterning and development as well as midbrain development. In the early stages of embryogenesis, FGF-8 is expressed in developing brains, limbs, heart, lung, skeleton, teeth, and the renal system. Application of FGF-8 to embryos induces the formation of brains and ectopic limbs, consistent with the role of FGF-8 in developmental processes. FGF-8-null mice have an embryonic lethal phenotype. In adult tissues, low levels of expression have been detected in heart, brain, lung, kidney, testis, prostate, and ovary.
The FGF-8 gene has 6 exons that potentially encode 8 isoforms. Seven isoforms of FGF-8 have been detected, with differences mapping to the N-terminal region (Blunt, A. G., et al. (1997) J. Biol. Chem. 272:3733-3738). The significance of these isoforms is unclear. FGF-8b displays the most potent mitogenic activity in vitro as compared to FGF-8a, -8c, -8d, -8e, -8f, and -8g isoforms (Blunt, A. G., et al., supra). FGF-8a does not stimulate mitogenesis through the known FGF receptors, unlike the other FGF-8 isoforms (Blunt, A. G., et al., supra). FGF-8 has been shown to modulate chondrogenesis (Moftah M, et al. (2002) Dev. Biol. September 15; 249(2):270) but the involvement of FGF-8 in bone formation is unknown.
FGF-8 is highly homologous to FGF-13, FGF-17, and FGF-18, containing more than 50% amino acid identity with each.